NextGen directed evolution: Decoding phage dark matter

Antibiotic resistance is a growing global health threat. Infections that were once easy to treat are becoming dangerous again because many bacteria have developed resistance to common antibiotics. This creates an urgent need for new ways to treat bacterial infections not only in human medicine, but also in agriculture and veterinary settings, where antibiotics are often widely used. One promising alternative is phage therapy. Phages, short for bacteriophages, are viruses that infect and kill bacteria. Because they are naturally occurring and highly specific to their bacterial targets, phages offer a form of treatment that can spare beneficial bacteria and reduce side effects. However, this very specificity also presents a challenge: each phage usually only works against a narrow group of bacteria. Matching the right phage to the right infection is currently slow and labor-intensive, making phage therapy difficult to scale up or use in urgent cases. This also makes it crucial to better understand phage genomes, how they work, how they evolve, and which genes determine whether a phage can infect a specific bacterial strain. This project aims to develop a new automated platform to train phages more quickly and efficiently. Using a small lab-on-a-chip device, we will evolve phages in the laboratory to better infect dangerous bacteria, especially those that are resistant to antibiotics. By continuously exposing phages to bacteria in a controlled, miniaturized environment, we hope to speed up the natural process of evolution and adapt phages within just a few days. The system will also allow us to study how phages evolve, how they swap genes, and how bacteria try to defend themselves. In doing so, we hope to gain new scientific insights that could lead to better treatment strategies. The tools and modules we develop will have the potential to modernize decade old traditional microbiology methods that are still defining phage research today. In the long run, this research could form the foundation for a tabletop system that doctors or veterinarians could use to prepare custom phage treatments directly at the point of care. This could significantly reduce the use of antibiotics and help slow the spread of resistance. The project brings together engineers, microbiologists, and medical researchers from the AIT Austrian Institute of Technology and the Medical University of Vienna. Together, we will try to build a system that combines clinical relevance with technological innovation and brings us one step closer to sustainable infection treatment in the post-antibiotic era.